Aging, a universal phenomenon of all living organisms is one of the least clearly understood biological processes. Medical advances in the last century have enable people in our society to live longer and to remain healthy for a significantly greater amount of time; therefore, it is crucial to elucidate the physiological and functional changes that occur in various organs with aging to adequately care for the elderly patients. With the support of this grant, we have made great strides in the better understanding of the physiologic changes that occur in the GI tract with aging. Our studies have proved invaluable in identifying important functional alterations that occur with age, such as dysregulation of intestinal mucosal and pancreatic growth, and response to trophic factors. Our studies have shown that aging affects GI hormones (expression, tissue content and secretion) and their target tissues. We have extended these initial studies to focus on changes occurring predominantly at the molecular level by assessing gene expression patterns over the full spectrum of aging. Furthermore, we have model novel observations regarding changes in the stress-related proteins (ie, heat-shock proteins) that occur in the GI tract, and, using a gene array analysis, have identified alterations in genes of the duodenum and colon of aged rats compared to young controls. Based on our findings, the central hypothesis of this proposal continues to e that aging in the GI tract results in changes in gene expression patterns which contribute to functional alterations noted with aging. To examine this hypothesis, we have planned experiments with the following Specific Aims: 1) To further define the changes in gene expression patterns in the GI tract associated with aging. We plan on conducting detailed studies regarding the developmental expression patterns of hormones and their receptors, the effects of aging on stress- related proteins, the changes in gene expression patterns by dietary alterations or gut position, and assessing an array of changes in gene expression patterns of hormones and their receptors, the effects of aging on stress-related proteins, the changes in gene expression patterns by dietary alterations or gut position, and assessing an array of changes in gene expression in the intestinal tract with aging. We plan on conducting detailed studies regarding the developmental expression patterns by dietary alterations or gut position, and assessing an array or changes in gene expression in the intestinal tract with aging. 2) To assess the functional effects of aging on intestinal and pancreatic growth. Under this aim, we plan to analyze in detail the effects of tropic factors and surgical models on intestinal growth with aging, and the mechanisms responsible for decreased pancreatic growth with aging. The studies in this current proposal will extend our previous finding by further delineating the molecular alterations that occur in the GI tract with aging and the functional consequences of these changes. Our studies will provide important and clinically relevant results regarding the functional consequences of aging in the GI tract.